The proposed studies will attempt to define the function of a family of lectin-like proteins, designated NKG2, that is expressed primarily on NK cells. All studies will be carried out on two family members, NKG2-A and NKG2-D, that have very different amino acid sequences throughout their lectin domains and, thus, probably have different ligand specificities. cDNA fragments encoding these two proteins will be introduced into a number of procaryotic and eucaryotic expression vectors to create reagents and cell lines for subsequent studies. Bacterial expression products will be used to immunize rabbits for the generation of polyclonal antibodies. Monoclonal antibodies will be generated against NKG2 lectin domains expressed either on the surface of COS or as secreted fusion proteins. A number of assays are planned to test for the ability of the NKG2 proteins, when bound either by the natural ligand or by anti-NKG2 monoclonal antibodies, to trigger a cytolytic response or deliver a transmembrane signal. These assays will be carried out on an NK cell population and on NKG2-transfected T cell lines. Eucaryotic expression products will also be used to identify cells that express the NKG2 target ligands.